Anthracyclines Questioned in HER2-negative Breast Cancer

According to an article recently published in the Journal of the National Cancer Institute, patients with human epidermal growth factor receptor-2 (HER2) negative breast cancer may not benefit from treatment including anthracyclines, a class of chemotherapy.

Early breast cancer (cancer that has not spread past the lymph nodes under the arms) has high cure rates following standard therapies. These cure rates are largely attributed to improvements in treatment, including chemotherapy. Standard treatment for early breast cancer typically includes surgical removal of the cancer, followed by radiation, chemotherapy, and/or hormone therapy. Chemotherapy followed by surgery in early breast cancer is referred to as adjuvant chemotherapy.

Approximately 25–30% of breast cancers are also referred to HER2-positive cancers. The HER2 is a protein found in biologic pathways that are involved in cellular replication and growth. If patients have an overabundance of HER2 or a mutation within a gene affecting HER2, they are classified as having HER2-positive cancer. As a treatment option, these patients may now receive the targeted agent Herceptin® (trastuzumab), which binds to HER2 and decreases or prevents cellular growth through this pathway.

HER2-negative breast cancers, on the other hand, do not have an overabundance or mutation of HER2, which makes treatments targeted against HER2 ineffective. Standard therapy for HER2-negative breast cancers typically includes the same treatment as for HER2-positive therapy, except without Herceptin or other drugs specifically targeted against HER2.

Chemotherapy also remains a cornerstone of treatment for patients with early breast cancer. A common class of chemotherapy agents used in combination with other therapies is anthracyclines. Anthracyclines refer to the chemotherapy agents Adriamycin® (doxorubicin), Ellence® (epirubicin), and Doxil® (liposomal doxorubicin). Although commonly used, anthracyclines are associated with side effects involving the heart, which are sometimes irreversible.

With the advent of more-individualized treatment approaches for many types of cancer, researchers are evaluating specific agents for the treatment of specific subgroups of patients. Goals of such individualized approaches include improving disease outcomes and allowing more patients to avoid side effects caused by unnecessary therapy.

Researchers from Italy recently conducted a large analysis of clinical trials that compared adjuvant chemotherapy regimens with and without anthracyclines for the treatment of early breast cancer. The researchers explored the efficacy of anthracyclines in respect to HER2 status (HER2-positive versus HER2-negative) among patients. This analysis included eight clinical studies including over 6,500 women.

Among patients with HER2-positive breast cancer, treatment with anthracyclines resulted in significantly superior cancer-free and overall survival compared with treatment that did not include anthracyclines.

Among patients with HER2-negative breast cancer, treatment with anthracyclines did not improve cancer-free or overall survival compared with treatment that did not include anthracyclines.

The researchers concluded: “The added benefits of adjuvant chemotherapy with anthracyclines appear to be confined to women who have HER2 [positive]” breast cancer. Patients diagnosed with breast cancer should discuss their HER2 status with their physicians, as well as the risks and benefits of all different treatment options.